Is Psychiatry Ready For Medical MDMA?

Within five years, science will likely have answered a controversial question: can methylenedioxymethamphetamine (MDMA) treat psychiatric disorders?

After some studies showing a positive effect, MDMA-assisted psychotherapy is entering final clinical trials as a treatment for post-traumatic stress disorder (PTSD). If these trials show positive results, MDMA will go from an illegal drug to a prescription medicine in the United States by 2021, potentially prompting movement in this space in Australia and Europe.

MDMA would move from the fringes to mainstream psychiatry, becoming recognised as a mainstream treatment option. What remains less clear is how psychiatry will deal with questions arising from this new treatment approach.

MDMA In Medicine: A Brief History

Better known as a street drug in the rave scene of the 1980s and ’90s, MDMA was used in the 1970s by a small band of US psychiatrists and therapists. This group believed it enhanced the therapeutic bond and improved treatment for ailments ranging from marital distress to, potentially, schizophrenia.

Following rebranding as “ecstasy”, large-scale recreational use of MDMA led to its 1985 listing as an illegal drug in the USA (Australia followed in 1986). The MDMA-therapy community unsuccessfully protested against this designation.

Advocates for MDMA-assisted psychotherapy have been playing the long game ever since, undertaking a painstaking process of research and advocacy, which has culminated in the upcoming trials.

MDMA Versus Ecstasy

Advocates for MDMA-assisted psychotherapy have been at pains to distinguish the street drug ecstasy from MDMA the medicine. Ecstasy can contain a range of substances as well as varying doses of MDMA.

This is unsurprising given early evidence that high repeated MDMA doses – more relevant for recreational than therapeutic use – damage serotonergic neurons in animals.

Catastrophic predictions of a lost generation of ecstasy users, however, failed to materialise. Indeed, numerous people have received MDMA doses similar to those proposed for therapy in laboratory studies. This shows that MDMA can be safely administered under controlled conditions to well-screened healthy adults.

It remains unknown whether the same is true of groups excluded from most studies. This includes children and older people, and those with psychiatric or physical illnesses. Studies to date do, however, suggest acceptable safety in adults with PTSD.

Pharmacologically Enhanced Treatment

One aspect of MDMA therapy attracting less attention is that it involves a fundamental shift in psychiatric medication. All currently approved psychiatric medications treat symptoms rather than the disease itself. Relapse is common after stopping treatment.

MDMA-assisted psychotherapy, by comparison, involves limited MDMA doses over two or three sessions of eight to ten hours. The aim is to “fast-track” psychotherapy to produce long-lasting changes.

Possible mechanisms of such an effect are unclear. One suggestion is that the effects of MDMA, such as feelings of empathy, openness and reduced fear, might allow people to reprocess traumatic memories during psychotherapy.

Other medications are also being considered as adjuncts for psychotherapy. These include potent psychoactives like LSD and psilocybin, or drugs thought to enhance psychotherapy via mechanisms other than psychoactive effects (e.g. d-cycloserine).

It is possible, however, that a broader range of pharmaceuticals could be used in this way. Thus, a potential benefit of MDMA’s approval could be to spur further research in this area.

The Challenges Of Regulation

The potential approval of MDMA for prescription gives rise to pressing questions about regulation. For instance, should prescribing be limited to physicians with specific qualifications? What training should be required for those conducting the psychotherapy? How should the drug be handled and stored by pharmacists?

The combination of a drug-affected patient with non-drug-affected therapists could make patients vulnerable during psychotherapy. This suggests a need for stringent training and oversight of MDMA-assisted therapy.

Approval of MDMA will also lead to off-label prescribing, with doctors prescribing the drug for conditions other than PTSD. This could include a range of conditions, such as depression and substance use disorders, and various patient groups.

A particular issue is prescribing to children/adolescents. To date no controlled studies have assessed the safety of MDMA in young people. Planned studies in adolescents with PTSD will thus be important.

Is Anything ‘Penicillin For The Soul’?

The slow progression of MDMA-assisted psychotherapy from the subcultural margins towards approval has been driven by the belief of those advocating for it.

Without this motivated community, MDMA would likely not have been developed as a medication, as it is off patent. The downside of this robust advocacy base is that it can lead to rather extreme claims (e.g. “penicillin for the soul”) and experimenter bias.

In addition to well-designed studies that control for experimenter bias, there is a need for researchers and clinicians outside the MDMA-advocacy community to be involved in the ongoing development of this research direction.

If MDMA is to become a part of mainstream psychiatry’s armamentarium, many questions will need to be answered. The next few years will be critical to see if MDMA joins the ranks of failed psychiatric treatments, or offers new hope to people suffering from PTSD.

Author: Gillinder Bedi, Assistant Professor of Clinical Psychology (in Psychiatry) University of Melbourne and Orygen National Centre of Excellent in Youth Mental Health, University of Melbourne. Image: ch1ris23. Licensed under CC-BY.